The aim of this study is to explore the therapeutic effect of Quintuple method in the treatment of patients with multiple and refractory liver metastases from colorectal cancer. A randomized single-arm clinical trial was conducted.The intervention group was treated with single SOX chemotherapy, SOX chemotherapy combined with cetuximab targeted therapy, SOX chemotherapy combined with low-dose cetuximab targeted therapy combined with three-drug regimen（Quintuple method）, and the RECIST 1.1 solid tumor evaluation criteria were used to assess the disease.

Patients with inoperable colorectal liver metastases were selected for genetic testing and enrolled if Kras/Nras/Braf wild-type was detected. The enrolled patients were randomly divided into three groups, in which patients in the single chemotherapy group were treated with SOX regimen alone for chemotherapy;patients in the chemotherapy targeted group were treated with SOX regimen chemotherapy combined with cetuximab targeted therapy; patients in the Quintuple method group were treated with SOX regimen chemotherapy,cetuximab targeted therapy and folic acid, vitamin A, and metronidazole three-drug regimen. Specific drugs were administered at the following doses: SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and S1 orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Metronidazole 0.4 g/time, qd; vitamin A 5,000 units/time, qd; folic acid 5 mg/time, qd. The latter three drugs were continued until the end of all chemotherapy cycles.Tumor markers associated with liver metastases from colorectal cancer,including magnetic resonance imaging and computed tomography, wererepeated every 3 months and disease was assessed using RECIST 1.1 criteria for the evaluation of solid tumors. The primary end point was death, and the secondary end point was disease progression.

Inclusion Criteria:

1. Aged 18-80 years at the time of signing the informed consent form;
2. Patients with histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
3. Patients with liver metastases found by imaging examination, and liver metastases cannot be radically resected, Or relapse liver metastasis;
4. At least one measurable metastatic lesion as defined by RECIST version 1.1;
5. Genetic test results are Kras/Nras/Braf wild-type or mutation type;
6. ECOG performance status 0-1;
7. Except for the liver, other organs function well;
8. Willingness and ability to comply with scheduled visits, treatment plans,laboratory tests, and other study procedures.

Exclusion Criteria:

1. Patients with non-primary intestinal cancer;
2. Patients whose primary tumor as well as metastases can be radically resected by surgery;
3. One or several serious allergies to each drug required for the trial;
4. Combined with respiratory, circulatory, urinary, hematopoietic and other serious underlying diseases.