Tislelizumab With Fruquintinib, Metronidazole, in Mismatch Repair-proficient or Microsatellite Stability, Advanced Colorectal Cancer: a Multicenter, Single Arm, Clinical Trial

Inclusion Criteria: 1. No gender limit, age ≥ 18 years old and ≤ 80 years old; 2. Colorectal cancer (AJCC stage IV) diagnosed by histological or cytological biopsy as metastatic or unresectable, with immunohistochemical or genetic testing indicating MSS or MSH-L type; 3. Treatment requires third line or above, has previously received standard first and second line treatment, and the disease has progressed after treatment; 4. Before accepting tirelizumab, qPCR should be used to detect the Fn deltaCT value ≥ -22.24 in fecal samples; 5. ECOG score: 0-1 points; 6. Baseline blood routine and biochemical indicators meet the following criteria (no blood transfusion or use of colony stimulating factors 2 weeks prior to screening) Blood routine: hemoglobin ≥ 90g/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 100 × 109/L Liver function: ALT and AST ≤ 2.5 x ULN, serum total bilirubin ≤ 1.5 x ULN (if there is liver metastasis, ALT and AST ≤ 5 x ULN, serum total bilirubin ≤ 3 x ULN), serum albumin ≥ 30g/L Renal function: serum creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance rate ≥ 50 mL/min (calculated according to Cockcroft Gault formula). 7. Those who voluntarily participate in the trial and sign an informed consent form. Exclusion Criteria: 1. Pregnant or lactating women; 2. Chronic intestinal diseases (such as Crohn's disease, ulcerative colitis, etc.), infectious intestinal diseases during the screening period, and intestinal obstruction during the screening period; 3. Subjects with poor control of hypertension (systolic blood pressure\>150 mmHg and/or diastolic blood pressure\>100 mmHg) and a history of hypertensive crisis or hypertensive brain disease; 4. Severe liver and kidney function or heart dysfunction; 5. Patients who use antibiotics for more than 5 days within one month prior to immunotherapy; 6. Patients with known brain or meningeal metastases, regardless of whether they have received treatment, are not eligible for inclusion in this trial. 7. Individuals with contraindications to the use of metronidazole medication; 8. Those who are unwilling to participate in the trial or sign informed consent forms; 9. The researchers believe that there are any situations that are not suitable for selection.