Phase II - Treatment Regimen Exploration Stage:

1. Evaluate the safety and efficacy of the following three treatment regimens:

   Liposomal irinotecan + 5-FU/LV + bevacizumab + Enlonstobart (Group A) Liposomal irinotecan + 5-FU/LV + bevacizumab (Group B) Irinotecan + 5-FU/LV + bevacizumab (Group C)

2. Provide a basis for selecting the treatment regimen for the confirmatory phase.

3. Explore the relationship between tumor tissue, stool, and blood biomarkers and efficacy and adverse reactions in liposomal irinotecan combination regimens versus irinotecan combination regimens.

Phase III - Efficacy Confirmation Stage:

Compare the efficacy and safety of liposomal irinotecan combination regimens versus irinotecan combination regimens in second-line treatment of metastatic colorectal cancer.

Inclusion Criteria:

1. Aged ≥ 18 years old and ≤ 75 years old.
2. Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma;
3. Patients must have at least one measurable lesion according to RECIST 1.1 criteria.
4. Had received first-line treatment based on oxaliplatin.
5. Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
6. Expected survival time ≥3 months.
7. Adequate organ function, meeting the following laboratory test standards:

1) Bone marrow function: Neutrophils≥1.5×109/L, Platelets≥100×109/L, Hemoglobin≥90 g/L, White blood cells ≥3.0×109/L; 2) Liver function:Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase≤2.5×upper limit of normal (ULN), when there is liver metastasis, ≤ 5×ULN; Total bilirubin≤1.5×ULN; 3) Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance rate ≥ 60 ml/min, Urine protein≤2+; 4) Coagulation function: Activated partial thromboplastin time and International Normalized Ratio ≤1.5 × ULN; 5) Thyroid function: Thyroid stimulating hormone≤ULN; If abnormal, additional tests for FT3 and FT4 should be conducted and their levels should be normal; 6) Albumin≥3 g/dL; 8. Pregnant women of childbearing age with negative pregnancy test and non-lactating, participants with reproductive capacity must receive effective contraceptive measures; 9. Patients and/or legal representative must have the ability to understand and voluntarily sign a written informed consent.

Exclusion Criteria:

1. Patients with a history of other malignancies within the past 5 years, except for cured carcinoma in situ or basal cell carcinoma of the skin.
2. Prior treatment with irinotecan or liposomal irinotecan-based chemotherapy, or prior treatment with immune checkpoint inhibitors (including but not limited to PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors).
3. Patients with left-sided colorectal cancer, RAS/BRAF wild-type, who did not receive cetuximab in first-line therapy.
4. Patients with known mismatch repair dysfunction or microsatellite instability ;
5. Patients with a large amount of pleural effusion or ascites that require drug intervention treatment;
6. Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, who show persistent signs/symptoms without improvement despite appropriate antimicrobial therapy.
7. Known active HIV infection; untreated active HBV or HCV infection.
8. Patients with uncontrolled systemic diseases, including: cardiac disease of NYHA Class II or above; uncontrolled hypertension (defined as systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg despite standard antihypertensive therapy) or a history of hypertensive crisis or hypertensive encephalopathy; uncontrolled diabetes mellitus; etc.
9. Patients with active autoimmune diseases, or with a history of autoimmune disease within 2 years prior to enrollment that still requires systemic therapy. Exceptions include participants with well-controlled type 1 diabetes, hypothyroidism controlled with hormone replacement alone, skin disorders not requiring systemic treatment, or those in whom recurrence is not anticipated in the absence of external triggers.
10. Patients with primary immunodeficiency diseases or with a history;
11. Patients who have received immunosuppressant treatment within 14 days before enrollment or require daily systemic steroid treatment (such as > 20 mg/day prednisone or equivalent drugs), except those treated with nasal, inhalation or other routes of local glucocorticoid therapy;
12. Patients with severe gastrointestinal diseases;
13. History of abdominal surgery, thoracic surgery, or intestinal resection within 28 days prior to enrollment.
14. Had interstitial lung disease or non-infectious pneumonia requiring glucocorticoid treatment;
15. Known hypersensitivity or intolerance to the investigational drugs or their excipients.
16. History of pulmonary hemorrhage or hemoptysis of grade 2 or higher (defined as at least 2.5 mL of bright red blood) within 1 month prior to enrollment.
17. History of arterial thromboembolism, severe bleeding (excluding surgical bleeding), or active thromboembolic or severe bleeding events within 6 months prior to enrollment.
18. Had symptomatic central nervous system metastasis;
19. Had strong inhibitors or inducers of CYP3A4, CYP2C8 and UGT1A1;
20. Receipt of intravenous antitumor therapy within 28 days, or oral antitumor medication within 14 days, prior to the first dose of study drug.
21. Patients judged by the investigator to be unsuitable to participate in this study.