Sintilimab Plus Bevacizumab and Chemotherapy in MSS/pMMR Colorectal With no Liver Metastasis

1. Sign written informed consent before implementing any experimental procedures

2. Over 18 years old

3. Histologically confirmed as colorectal adenocarcinoma without liver metastasis

4. At least one measurable lesion (RECIST 1.1)

5. Satellite stable (MSS) or low instability (MSI-L) or normal expression of DNA mismatch repair genes (pMMR)

6. ECOG PS score is 0-1

7. Progress after initial treatment or standard first-line treatment

8. Have sufficient organ and bone marrow function

9. Expected to survive for more than 3 months

10. Participants must have normal hematological test results, including：

11. Participants' prothrombin time (PT) must be less than 1.5 times the upper limit of normal values, and activated partial thromboplastin time (APTT) must be less than 1.5% of the upper limit of abnormal values

12. Participants must have normal laboratory test results, including：serum creatinine levels less than or equal to 1.5 times the upper limit of the normal reference range, or creatinine clearance rates greater than 50 ml/min

13. For participants without liver metastasis, their alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels must be less than or equal to 2.5 times the upper limit of the normal reference range, and their serum total bilirubin levels must be less than 1.5 times the upper limit of the normal reference range

14. For female subjects of childbearing age, a urine or serum pregnancy test with negative results should be conducted within 3 days prior to the first administration of the study drug (Day 1 of the first cycle)

15. If there is a risk of conception, all subjects must use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period until 120 days after the last administration of the study drug

16. The subjects must agree to provide sufficient tumor tissue samples for PD-L1 expression detection

1. Known presence of active central nervous system (CNS) metastases and/or cancerous meningitis

2. Microsatellite instability (MSI-H) or loss of expression of DNA mismatch repair genes (dMMR)

3. Currently participating in interventional clinical research treatment, or having received other research drugs or used research instruments for treatment within 4 weeks before the first administration

4. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors

5. Within 2 years prior to the first administration, there has been an active autoimmune disease requiring systemic treatment

6. Imaging shows tumor invasion/infiltration into large blood vessels, or researchers or radiologists assess a tendency towards bleeding

7. Have undergone major surgical treatment within 4 weeks prior to the initial administration of the investigational drug (excluding surgery for biopsy purposes) or are expected to undergo major surgery during the study period

8. Severe unhealed wounds, ulcers, or fractures

9. Undertook minor surgeries within 48 hours prior to the first receipt of the study drug

10. Currently or recently (within 10 days prior to receiving the first dose of the study drug) using aspirin (>325 mg/day) or other known nonsteroidal anti-inflammatory drugs that can inhibit platelet function for 10 consecutive days

11. Currently or recently (within 10 days prior to receiving the first dose of the study drug), using full dose oral or parenteral anticoagulants or thrombolytic agents for treatment for 10 consecutive days

12. There is a genetic tendency for bleeding or coagulation dysfunction, or a history of thrombosis

13. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation

14. Individuals known to be allergic to the active ingredients of the study drug

15. Prior to commencing treatment, the individual has not fully recovered from any toxicity and/or complications caused by any intervention measures (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss)

16. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive)

17. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center)

18. Pregnant or lactating women

19. The presence of any serious or uncontrollable systemic disease

21. Other situations that the researchers believe are not suitable for inclusion, or other potential risks that are not suitable for participation in this study