Background: The standard treatment of recurrent or unresectable pancreatic cancer is gemcitabine-based chemotherapy, combination with tarceva or capecitabine. However, there is no effective regimen for patients who have progressive disease after these drugs. We performed retrospective analysis to evaluate the efficacy and toxicity of ECF regimen for the patients who had good performance status but progressive disease after previous chemotherapy in recurrent or unresectable pancreatic cancer. Method: Between October 2008 and June 2011, we retrospectively reviewed twenty one patients who had an initially metastatic disease or recurrent disease after operation. All patients had progressive disease after the gemcitabine-based chemotherapy and a good performance status(ECOG≤2). The treatment schedules were as follows: 5-fluorouracil 1000 mg/m2, day 1-3, Cisplatin 60 mg/m2, day 1, and Epirubicin 50 mg/m2, day 1, repeated every 21 days. Result: Among the 21 patients, male was 13 patients and female was 8 patients. Median age was 59, and median ECOG P.S was 1. They were treated with gemcitabine/tarceva, gemcitabine/capecitabine,gemcitabine/5-FU or gemcitabine monotherapy as first line treatment. Median number of cycle was 2(range: 1-8). Six patients had stable disease, and two patients had partial response (overall response rate: 10%). The median progression free survival was 2.3 months, and the median overall survival was 4.3 months. In hematologic toxicity, there were 48% grade 3/4 neutropenia, and 10% thrombocytopenia. In non-hematologic toxicity, there were 5% grade 3 nausea/vomiting, and fatigue. There was no treatment-related death. Conclusion: ECF regimen have been used for the refractory pancreatic cancer because this drugs was commonly used before the development of gemcitabine. In the present study, ECF showed little efficacy with the high rate of grade 3/4 neutropenia. Newer chemotherapeutic regimen should be developed for the patients with refractory pancreatic cancer but good performance status.