Purpose: The objectives of study are to evaluate efficacy and toxicity of combination chemotherapy FOLFIRINOX in Egyptian patients with inoperable or metastatic pancreatic cancer. Patients and Methods: Between September 2011 and September 2012, twenty patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were included to receive FOLFIRINOX protocol as first-line therapy. The median age was 54 years,. The majority of patients (70%) had metastatic disease. The median over all treatment period was 14 weeks (range: 8-26 weeks).A total of 168 cycles were administered with a median of 8 cycles (range 4-12) per patient. Results: Over all response rate was 65 % (PR 35%+SD30%). Median Progression Free Survival was 6 months (95% CI: 5.782-6.218). Progression-free survival rates at 6 and 12 months were 73 % and 10% respectively. Median overall survival was 10.5 months (95% CI: 8.309-12.691). Overall survival rates at 6 and 12 months were 84 % and 40% respectively. Grade 3-4 chemotherapy-related toxicities were observed in 30% of patients. Conclusion: The combination of FOLFORINOX had significant improvement in response rate, progression free survival and overall survival in spite of significant manageable toxicity.