Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. However，in colorectal cancer (CRC), the role of HRD alterations is mostly unknown. This study aims to explore the the Efficacy and Safety of Fluzoparib combined with Irinotecan in the Second-line treatment of HRD alterations metastatic colorectal cancer.

Study protocol for an open-label, single-arm, phase II study of combination of Fluzoparib and rinotecan as the second-line treatment for patients with HRD alterations metastatic colorectal cancer (mCRC). Patients will receive Fluzoparib combined with Irinotecan treatment protocol, which included irinotecan asintravenous infusion at 180mg/m2 (on day 1) and Fluzoparib 150mg capsules given bid (days 1-7) every 2 weeks.

Inclusion Criteria:

• 18-75 years；
• Histological or cytological confirmed metastatic colorectal cancer;
• HRD alterations（inclued BRCA1/2、ATM、CDK12、PALB2、Check2、RAD51C、RAD51D etc.）；
• Intolerability toxicity occurs 8 weeks within first-line therapy;
• ECOG PS 0-1;
• Adequate hepatic, renal, heart, and hematologic functions;
• Negative serum pregnancy test at screening for women of childbearing potential;
• Informed consent was signed before the study began.

Exclusion Criteria:

• Prior treatment with PARPi drugs；
• Symptomatic brain or meningeal metastases；
• Patients have received local radiotherapy within 1 month prior to treatment;
• Patients who had active bleeding or coagulopathy before enrollment, had a tendency to bleed, or were receiving thrombolytic therapy and were considered by the investigator to be ineligible for enrollment;
• Women who are pregnant (with a positive pregnancy test before medication) or breastfeeding;
• Expected survival <3 months;
• Received other investigational drugs within 4 weeks prior to treatment;
• Patients who had active uncontrollable neurological, mental disease or mental disorder, poor compliance, unable to cooperate and describe the treatment response;
• Allergy to the study drug or any of its excipients;