TPS225 Background: Immune checkpoint inhibitors monotherapy has limited clinical benefits in patients with MSS or pMMR metastatic colorectal cancer (CRC), which may be attributed to low level of tumor-infiltrating lymphocytes in MSS advanced CRC. Combination immunotherapy is changing the landscape of cancer treatment, especially combination of immunotherapy with small molecule angiogenesis inhibitors. Preclinical studies have shown that there is a time window from anti-angiogenesis to vascular normalization and this has been initially demonstrated in the clinical study of breast cancer. However, the time window is rarely considered in clinical practice. It is necessary to explore the optimal administration timing of angiogenesis inhibitors when combined with immunotherapy. Here, we conduct an open-label, single-center, phase II study to explore the issue. Methods: Patients eligible for the trial are included: 1) pathologically confirmed advanced colon or rectal adenocarcinoma, MSS or pMMR; 2) previously received only 2 standard regimens after recurrence or metastasis; 3) aged 18-70 years (boundary value included); 4) ECOG performance status of 0 or 1; 5) at least 3 months of survival expectations; 6) patient must present with measurable lesions according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST version 1.1; 7) patients with asymptomatic central nervous system metastases or asymptomatic brain metastases after treatment, with stable disease for at least 3 months, and need not be treated with steroids for at least 4 weeks; 8) had adequate organ function before the enrollment; 9) patients of reproductive age should agree to use effective contraceptive measures from the time of signing the informed form until 3 months after the last dose; 10) sign an informed consent form voluntarily, and be willing to and be able to follow and complete all experimental procedures. The patients enrolled were given oral fruquintinib (3 mg, qd, for 2 consecutive weeks, and then discontinued for 1 week, in 3 weeks [21 days] cycle); on the day 5, administered with intravenous camrelizumab (200mg, once every 3 weeks). The treatment was administered continuously until disease progression, unacceptable toxicity, or required withdrawal from patients. The primary endpoint is progression free survival (PFS), and the secondary endpoints are overall survival (OS), objective response rate (ORR), disease control rate (DCR) and drug safety. As of September 23, 2021, a total of 21 patients have been enrolled. Clinical trial information: ChiCTR2100048528.