Chemotherapy Plus Bevacizumab and Anti-PD-1 Followed by Induction Therapy of Chemotherapy Plus Bevacizumab

1. The patient volunteered to participate in the study, signed the informed consent form, and had good compliance.
2. Age: 18-75 years old (including 18 years old and 75 years old).
3. Body weight of 40kg.
4. Metastatic colorectal cancer confirmed by histology and / or cytology and initially unresectable.
5. MSS type or pMMR.
6. Patients are required to have at least one measurable lesion (RECIST 1.1).
7. ECOG physical strength status: 0-1 point.
8. Expected survival of 12 weeks.

9. Blood test (no transfusion within 14 days, no correction with granulocyte colony stimulating factor or other hematopoietic stimulating factor within 7 days before the laboratory test)

   1. Absolute neutrophil value of 1.5109/ L, platelet 1010109/ L, hemoglobin concentration of 9 g/dL);
   2. Liver function test (bilirubin 1.5 ULN; aspartate aminase and glutamate aminase 2.5 ULN, AST and ALT 5 ULN);
   3. Renal function (serum creatinine 1.5 ULN or creatinine clearance (CCr) 60 mL/min);
   4. Coagulation (international normalized ratio (INR) 1.5 ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) 1.5 ULN);
   5. Thyroid function, upper limit of normal (TSH); if abnormal, FT3 and FT4 levels should be examined, normal FT3 and FT4 levels can be included.
10. Women of childbearing age must have a negative serum pregnancy test within 14 days before treatment and be willing to use medically approved effective contraception (e. g., IU, contraceptives or condoms) during 3 months after the study and the last study drug; surgical sterilization for male subjects with a woman of childbearing age, or effective contraception is recommended during the study and 3 months after the last study dose.

Exclusion Criteria:

1. Have received the following treatments within the first 4 weeks of treatment: tumor radiotherapy, surgery, chemotherapy, immune or molecular targeted therapy, and other clinical study drugs.
2. Active autoimmune diseases requiring systemic treatment (i. e., corticosteroids or immunosuppressive agents) have occurred in the past 2 years. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered systemic treatment.
3. Diagnosis with immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first treatment. A physiological dose of corticosteroids may be approved after consultation with the investigator.
4. Previous small molecule targeted drug therapy, such as fuquintinib, etc.
5. Previous treatment with an oxaliplatin-based chemotherapy regimen.
6. Symptomatic brain or meningeal metastases.
7. Metastatic colorectal cancer with either MSI-H or dMMR.
8. Severe infection (e. g. intravenous infusion of antibiotics, antifungals or antiviral drugs), or unexplained fever> 38.5℃ during screening / first dose.
9. Hypertension that is not well controlled with antihypertensive medication (systolic 140 mmHg or diastolic 90 mmHg).
10. Significant clinical bleeding symptoms or significant bleeding tendency (bleeding> 30 mL, hematemesis, black feces, stool within 3 months), hemoptysis (> 5 mL of fresh blood within 4 weeks); or venous / venous thrombosis events within 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; or long-term anticoagulation with Chinese standard or heparin, or long-term antiplatelet therapy (aspirin 300 mg / day or clopidogrel 75 mg / day).
11. During screening, the tumor was found to invade large vascular structures, such as pulmonary artery, superior vena cava vein or inferior vena cava vein, which was judged to be at risk of large bleeding by the investigators.
12. Active heart disease, including myocardial infarction, severe / unstable angina, within 6 months before treatment. Echocardiography showed a left ventricular ejection fraction of \<50%, and the arrhythmia was poorly controlled.
13. Other malignancies within or during the previous 5 years (except for cured skin basal cell carcinoma and carcinoma of the cervix in situ).
14. Known allergy to the study drug or any of its excipients.
15. Active or uncontrolled serious infection; A)known human immunodeficiency virus (HIV) infection; B) known history of clinically significant liver disease, including: viral hepatitis [known hepatitis B virus (HBV) carriers must exclude active HBV infection, namely HBV DNA positive (> 1104 copies / mL or> 2000 IU / mL); known hepatitis C virus infection (HCV) and HCV RNA positive (> 1103 copies / mL)], or other hepatitis, cirrhosis;
16. Any other disease, clinically significant metabolic abnormalities abnormal physical examination or laboratory abnormalities, according to the investigator, there is reason to suspect a disease or state is not suitable for the study drug (such as seizures and need treatment), or will affect the interpretation of the results, or make the patient in a high risk situation.
17. Routine urine indicates urine protein 2 +, and 24-hour urine protein quantification> 1.0g.