Limited agents are optional after standard first and second line treatment for mCRC. Nowadays, cancer therapy has entered the era of immunotherapy. The approved cancer therapies include pembrolizumab and nivolumab, but only for MSI-H patients. 95% of non MSI-H / dMMR patients with advanced colorectal cancer can not benefit from them. Therefore, the use of PD-1 / PD-L1 monoclonal antibody in mCRC is greatly limited. Our previous research showed that anti-PD-1 combined with Fruquintinib can significantly inhibit the growth of CRC in MSS mice. At the same time, a retrospective clinical study showed that patients with MSS CRC can benefit from Sintilimab combined with Fruquintinib. Camrelizumab is PD-1 monoclonal antibody, which has been approved for a variety of tumors. The prospective clinical trial of Camrelizumab combined with Fruquintinib may bring new hope for the treatment of non MSI-H / dMMR patients with mCRC.This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

Our previous research showed that anti-PD-1 combined with Fruquintinib can significantly inhibit the growth of CRC in MSS mice. At the same time, a retrospective clinical study showed that patients with MSS CRC can benefit from Sintilimab combined with Fruquintinib. Camrelizumab is PD-1 monoclonal antibody, which has been approved for a variety of tumors. The prospective clinical trial of Camrelizumab combined with Fruquintinib may bring new hope for the treatment of non MSI-H / dMMR patients with mCRC.This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

Inclusion Criteria:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
• Subjects with non MSI-H / dMMR metastatic colorectal cancer(CRC) (Stage IV)
• Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan.
• Subjects must not have been treated with Fruquitinib or any anti-PD-1 inhibitors.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary.
• Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol.
• Assigned informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Life expectancy of at least 3 months.
• Subjects must complete the treatment and follow-up on schedule according to the research plan.
• No brain metastasis, no spinal cord compression.
• Subjects agree to use blood samples for study analysis.
• Women of childbearing age must be negative in pregnancy test and willing to take effective contraceptive measures during the study period.

Exclusion Criteria:

• Subjects are severe malnutrition or need tube feeding.
• Radiotherapy or surgery has been performed within 30 days before treatment.
• Previous treatment with anti-PD-1 / PD-L1 inhibitor and / or fruquitinib.
• Other malignant tumors within 2 years and without cure (except for cured basal cell carcinoma of skin and carcinoma in situ of cervix);
• Subjects have active autoimmune system diseases、systemic hormone therapy or anti autoimmune drug therapy.
• Subjects with immunodeficiency or receiving systemic steroid therapy (prednisone > 10 mg / day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days before the first dose of combination therapy in this study;
• Subjects with active infection and still need systemic treatment 7 days before the first dose of therapy in this study.
• Subjects with uncontrollable systemic diabetes.
• Subjects with interstitial lung disease, non infectious pneumonia or pulmonary fibrosis;
• Subjects who have received allogeneic organ or stem cell transplantation in the past.
• Subjects allergic to the drugs or related components involved in this study.
• Are participating in other interventional clinical studies.
• The previous anti-tumor related adverses do not return to grade 1 in CTCAE before the first combination therapy.
• Subjects who have uncontrolled hypertension by drugs, that is, systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg.
• Thrombotic or hemorrhagic tendency or history within 60 days before the first medication, regardless of the severity.
• Any serious or unstable medical condition、mental illness or known active alcohol or drug abuse or dependence.