 Given the therapeutic potential and reduced toxicity advantages of S-1 compared with other fluoropyrimidines, this trial assessing S-1 with Oxaliplatin plus Irinotecan is warranted for future investigations Phase II-III. The primary objectives are to determine the Maximal Tolerated Dose MTD, the Dose Limitant Toxicities DLTs and the safety profile of S-1 combined with fixed doses of Irinotecan SIRI schedule and fixed doses of Irinotecan and Oxaliplatin SIRINOX schedule. 