• Age ≥ 18 years, any gender;

• Histologically confirmed metastatic colorectal cancer (Stage IV, UICC), with initially unresectable metastases or refusal of surgery;

‣ Primary tumor located in the distal transverse colon, descending colon, sigmoid colon, and rectum, and RAS (KRAS and NRAS) and BRAF wild-type (Cohorts A and B);

⁃ Primary tumor located in the cecum, ascending colon, and proximal transverse colon, and RAS (KRAS and NRAS) mutant-type (Cohorts C and D);

• Treatment-naive patients who have not received standard anti-tumor therapy;

• At least one measurable tumor lesion per RECIST 1.1 criteria;

• ECOG performance status of 0-1;

• Patients with an expected survival time of ≥ 3 months and good organ function:

‣ (1) Neutrophils ≥ 1.5 \* 10\^9/L; platelets ≥ 100 \* 10\^9/L; hemoglobin ≥ 9 g/dL; serum albumin ≥ 3 g/dL;

⁃ (2) Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), T3 and T4 within normal ranges;

⁃ (3) Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 2 times ULN;

⁃ (4) Serum creatinine ≤ 1.5 times ULN, creatinine clearance rate ≥ 60 mL/min;

⁃ (5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN, unless the patient is receiving anticoagulant therapy and PT is within the expected therapeutic range of anticoagulants;

⁃ (6) Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN;

• Female patients of childbearing potential must have a negative pregnancy test; female patients not of childbearing potential; male patients of reproductive potential and female patients of reproductive potential and at risk of pregnancy must agree to use adequate contraception throughout the study period, continuing until 12 months after the last dose of study treatment;

• Signed and dated informed consent form indicating that the patient has been informed of all pertinent aspects of the study;

• Patients willing and able to comply with visit schedule, treatment plan, laboratory tests, and other study procedures.