The goal of this single-arm study is to evaluate the efficacy and safety of Envafolimab combined with Trifluridine/Tipiracil and Bevacizumab in the treatment of metastatic colorectal cancer patients who are refractory or intolerant to standard therapy.

Inclusion Criteria:

• Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection.

• Histologically or cytologically documented diagnosis of metastatic colorectal cancer refractory to second-line and above standard treatment; presence of at least one measurable lesions which should be measured on CT or MRI following RECIST 1.1 criteria.

• ECOG (Eastern Cooperative Oncology Group) performance status 0-2.

• Life expectancy of at least 3 months.

• Patient had no serious hematologic,hepatic, or renal abnormalities, and the results within a week were consistent with the following laboratory tests:

  1. Hematological Parameters: Neutrophil count ≥1.5×109/L;Platelets ≥80×109/L;Hemoglobin≥90g/L.
  2. Hepatic Function Parameters: AST and ALT ≤2.5×upper limit of normal（≤5×ULN if liver metastasis present）; Bilirubin ≤2.5 ×upper limit of normal.
  3. Renal Function Parameters: Cr ≤ 1.5×upper limit of normal.
  4. Coagulation Function Parameters: International Normalized Ratio (INR)≤1.5 or prothrombin time (PT)≤1.5×ULN or activated partial prothrombin time (APTT)≤1.5×ULN.
  5. Urinary protein≤1+, 24-hour urinary protein quantity ≤1.0g.

Exclusion Criteria:

• Symptomatic or known central nervous system metastases (head CT or MRI is not required to rule out brain metastases). For patients with suspected neurological metastasis, head CT or MRI should be performed within 28 days before enrollment to rule out neurological metastasis.
• The target lesion was treated locally within 3 months.
• There are neurological or psychiatric abnormalities that affect cognitive ability.
• Subjects with hypertension not well controlled by single antihypertensive medication (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg); Patients with history of unstable angina pectoris; Patients with newly diagnosed angina pectoris or myocardial infarction within 3 months prior to screening; Arrhythmias (including QTcF: ≥450 ms in men and ≥470 ms inwomen) require long-term use of antiarrhythmic drugs and New York Heart Association grade ≥II cardiac insufficiency.
• Prior or combined history of other malignancies, with the exception of cured basal cell carcinoma of the skin,carcinoma in situ of the cervix, and other early tumors that are expected to be free of recurrence within six months after radical treatment.
• Patients currently receiving or having received anticancer therapies within 4 weeks prior to the enrollment.
• For female subjects: should be surgically sterilized, postmenopausal, or consent to use a medically approved contraceptive during the study treatment and for 6 months after the end of the study treatment period; Serum or urine pregnancy tests must be negative within 7days prior to study enrollment and must be non-lactating. Male subjects: Patients who should be surgically sterilized or who have consented to use a medically approved contraceptive method during the study treatment period and for 6 months after the end of the study treatment period.
• There are multiple factors that affect oral medications (such as inability to swallow,chronic diarrhea, and intestinal obstruction).
• Patients with active bleeding, long-term unhealed wounds, and any surgical procedures within 2 months.
• Any arteriovenous thrombosis event occurred within 6 months, including cerebrovascular accident, deep vein thrombosis (deep vein thrombosis caused by the installation of a deep vein catheter in the previous chemotherapy, except for those who were judged to have recovered by the investigator), and pulmonary embolism.
• Severe chest and abdominal fluid, requiring clinical intervention.
• Have thyroid dysfunction that cannot be maintained within the normal range despite medication.
• History of immune deficiency or organ transplantation.
• There were other concomitant diseases that the investigators determined to seriously endanger the patient's safety or interfere with the patient's completion of the study.