The Combination of Fruquintinib, Tislelizumab and Stereotactic Ablative Radiotherapy in Metastatic Colorectal Cancer(RIFLE)

Inclusion Criteria:

* Aged over 18 years old, regardless of gender
* Fully informed and willing to provide written informed consent for the trial
* ECOG performance status 0-1
* Has an investigator determined life expectancy of at least 6 months
* Histologically or cytologically confirmed stage IV colorectal cancer (UICC 8th version)
* Has at least 2 measurable oligometastatic lesions on imaging (RECIST version 1.1). One will be treated with SABR and the other will be biopsied and evaluated against RECIST 1.1.
* Has progressive disease after receiving first-line standard antitumor therapy (chemotherapeutic agents including fluorouracil, oxaliplatin and irinotecan); previous neoadjuvant or adjuvant pelvic area radiotherapy is allowed; subjects included in the safety introduction phase may include third-line treatment or above, but these subjects will not be included in the final statistical analysis.
* Subjects receiving adjuvant oxaliplatin should progress during adjuvant therapy or within 6 months after completion.
* Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
* Subjects who withdraw from standard treatment before disease progressing due to unacceptable toxicity and exclude the use of the same drug are also allowed to be included.
* Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.

Exclusion Criteria:

* Pregnant or lactating women
* 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 tumor (non-invasive tumor, or carcinoma in situ, or T1)
* Baseline laboratory indicators do not meet the following criteria: neutrophils ≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L , ALT ≤2.5 ULN, AST ≤2.5 ULN, Cr≤ 1.5 ULN or creatinine clearance rate \<50ml/min, TBIL ≤1.5 ULN, APTT ≤1.5 ULN, PT ≤1.5 ULN (the criteria of patients with liver metastasis: PLT ≥80×10\^9/L, ALT ≤5 ULN, AST ≤5 ULN, TBIL ≤2.5 ULN)
* Serious electrolyte abnormalities
* Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h
* Uncontrolled hypertension: SBP \>140mmHg or DBP \> 90mmHg
* Receiving radiotherapy within 4 weeks
* Receiving anti-VEGF or anti-EGFR therapy within 4 weeks
* Stroke event or transient ischemic attack occurred within 12 months
* 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 histroy 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
* Previous treatment with immunotherapy or fruquintinib
* The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumors 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 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
* Serious mental abnormalities