Abstract: Objective To evaluate the efficacy and safety of FOLFIRI as second-line chemotherapy for advanced duodenal cancer. Methods Patients with advanced duodenal cancer who have failed to first-line therapy from June 2008 to January 2016 were analyzed retrospectively. Nine patients received FOLFIRI regiments as second-line chemotherapy. The efficacy and safety were evaluated by RECIST 1.1 and NCI-CTC 4.0 criteria. Overall survival （OS） and progression-free survival （PFS） were analyzed by Kaplan-Meier method. Results All patients were available for evaluating toxicity and effectiveness. The total treatment cycle was 41， and the median treatment cycle was 4（3-8 cycles）. The response rate was 11.1％ and disease control rate was 66.7％， including 1 case of PR， 5 cases of SD and 3 cases of PD. The median OS was 19.3 months and the median PFS was 6.5 months. The major treatment-related side effects including leucopenia， neutropenia， anemia， fatigue， nausea and etc， were mainly in grade 1-grade 2. Conclusion FOLFIRI is effective and tolerable in advanced duodenal cancer as second-line chemotherapy.