This is a single-center, open-label, single-arm, exploratory phase II clinical trial designed to evaluate the preliminary efficacy and safety of sintilimab in combination with oral gossypol acetate in patients with advanced pMMR/MSS colorectal cancer after failure of at least two prior lines of standard therapy. Eligible participants will have histologically or cytologically confirmed advanced colorectal adenocarcinoma, measurable disease according to RECIST version 1.1, ECOG performance status of 0 or 1, and adequate organ function. Participants will receive oral gossypol acetate once daily, followed by sintilimab administered intravenously every 3 weeks after a gossypol acetate lead-in period. The primary outcome is objective response rate assessed by RECIST version 1.1. Secondary outcomes include disease control rate, progression-free survival, overall survival, duration of response, and safety.

Inclusion Criteria:

1. Written informed consent provided before any study-specific procedures.
2. Age 18 to 75 years, male or female.
3. Histologically or cytologically confirmed advanced colorectal adenocarcinoma.
4. Confirmed pMMR/MSS tumor status. Participants without documented MSI/MMR status must undergo MSI or MMR testing during screening.
5. Disease progression after at least two prior lines of standard therapy.
6. Availability of tumor tissue suitable for pathological evaluation and biomarker analysis.
7. ECOG performance status of 0 or 1 within 7 days before the first dose of study treatment.
8. At least one measurable lesion according to RECIST version 1.1.
9. Adequate hematologic, hepatic, renal, coagulation, and organ function as defined in the protocol.
10. Female participants of childbearing potential must have a negative pregnancy test before initiation of study treatment and agree to use effective contraception during the study and for the protocol-specified period after the last dose.

Exclusion Criteria:

1. Histology of small cell carcinoma, squamous cell carcinoma, or mixed carcinoma.
2. dMMR/MSI-H tumor status.
3. Complete bowel obstruction or clinical conditions likely to progress to bowel obstruction.
4. Suspected bowel perforation based on clinical symptoms or imaging.
5. History of malignancy other than colorectal cancer within 3 years before screening, except malignancies with negligible risk of metastasis or death and treated with expected curative outcome.
6. Active autoimmune disease, history of autoimmune disease, or immunodeficiency requiring systemic treatment, except protocol-allowed conditions.
7. Significant cardiovascular disease within 3 months before initiation of study treatment, including New York Heart Association class II or higher heart disease, myocardial infarction, cerebrovascular accident, unstable arrhythmia, or unstable angina.
8. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT.
9. Severe chronic or active infection within 4 weeks before initiation of study treatment.
10. Active tuberculosis infection or inadequately treated prior active tuberculosis.
11. Active hepatitis B or hepatitis C infection as defined by protocol criteria.
12. Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
13. History of leptomeningeal disease.
14. Prior treatment with CD137 agonists, T-cell co-stimulatory agents, or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-TIGIT antibodies.
15. Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives before initiation of study treatment, whichever is longer.
16. Treatment with systemic immunosuppressive medications within 2 weeks before initiation of study treatment, except protocol-allowed medications.
17. Prior allogeneic stem cell transplantation or solid organ transplantation.
18. Receipt of a live attenuated vaccine within 4 weeks before initiation of study treatment or expected need for such vaccination during the study or within 5 months after the last dose of sintilimab.
19. Major surgery or severe traumatic injury within 28 days before initiation of study treatment, abdominal surgery or abdominal intervention within 60 days before initiation of study treatment, or expected need for major surgery during the study.
20. Receipt of any other investigational drug within 28 days before initiation of study treatment.
21. Known contraindication, hypersensitivity, or severe allergic reaction to any study drug or its excipients.
22. Pregnancy, breastfeeding, or intention to become pregnant during the study or within 5 months after the last dose of sintilimab.
23. Any other disease, laboratory abnormality, social condition, or medical condition that, in the investigator's judgment, may compromise participant safety, interfere with study compliance, or affect interpretation of study results.