Background: The majority of patients with gastroesophageal cancer present with inoperable or metastatic disease. After failure of first-line chemotherapy, ramucirumab is a proven option as monotherapy and in combination with paclitaxel as second line treatment in advanced gastric cancer. Irinotecan has shown significant improvement of overall survival compared to best supportive care (BSC) in the second line setting and is an accepted safe and efficient standard chemotherapeutic treatment for patients with refractory gastroesophageal cancer. More and more patients get treated with taxanes in the perioperative or 1st line metastatic setting. For those patients the benefit of a combination of ramucirumab and paclitaxel is unclear, and many physicians would choose an irinotecan based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a prospective, multicenter, randomized, investigator initiated phase II trial. Patients with advanced gastric or esophagogastric junction cancer will be randomized 2:1 to FOLFIRI (irinotecan 180 mg/m²; 5-FU 400 mg/m²; leucovorin 400 mg/m²; 5-FU 2400 mg/m² on day 1 and 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m² (days 1, 8, 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm B). Primary endpoint of the trial is OS rate after 6 months, based on the ITT population. The experimental therapy (FOLFIRI + Ramucirumab; n = 67) is considered to be a highly promising candidate for further development (e.g. in a phase III trial), if the true OS rate amounts to 65% or more, as this corresponds to the efficacy of the standard ramucirumab-paclitaxel regimen according to the RAINBOW study in the western population. Secondary endpoints are progression-free survival, response rate, safety and tolerability. Currently (Jan 2017) 40 of planned 111 patients are randomized. Clinical trial information: NCT03081143