Standard Systemic Therapy Combined With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer

Inclusion Criteria: Age between18 and 75 years old. An Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum. At least one evaluable metastatic lesion for radiotherapy and evaluation according to RECIST 1.1. Treatment naive (first-line cohort) and progressed on after first-line therapy or stopped first-line therapy due to unacceptable toxic effects (second-line cohort). Prior radiotherapy completed at least 4 weeks before enrollment. Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN. Sign the informed consent and have good compliance. Exclusion Criteria: Neutrophil \< 1.5×10\^9/L, PLT \< 100×10\^9/L (PLT \< 80×10\^9/L in patients with liver metastasis), or Hb \< 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria. TBIL \> 1.5 ULN, or TBIL \> 2.5 ULN in patients with liver metastasis. AST or ALT \> 2.5 ULN, or ALT and / or AST \> 5 ULN in patients with liver metastasis. Cr \> 1.5 ULN, or creatinine clearance \< 50ml / min (calculated according to Cockcroft Gault formula). APTT \> 1.5 ULN, PT \> 1.5 ULN (subject to the normal value of the clinical trial research center). Serious electrolyte abnormalities. Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h. Uncontrolled hypertension: SBP \>140mmHg or DBP \> 90mmHg. The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment. A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months. A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF\<50%). Uncontrolled malignant pleural effusion, ascites, or pericardial effusion. History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy. The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1). A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10\^4/ml), HCV infection or HCV DNA positive(≥1×10\^3/ml) and liver cirrhosis. Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period. The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems. Serious mental abnormalities. The diameter of brain metastasis is greater than 3cm or the total volume is greater than 30cc. Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm of the spinal cord on MRI.