Background: Periop. FLOT has become SOC for resectable, esophagogastric adenocarcinoma. However, patient’s outcome is still poor. This trial evaluates the addition of the VEGF-R2 inhibitor ramucirumab (RAM) to FLOT for resectable patients (pts). Methods: This is a prospective, international, randomized, investigator-initiated phase II/III trial. Pts with resectable, Her2-negative, adenocarcinoma of the stomach and GEJ (≥ cT2 or cN+) were enrolled. Pts were randomized to 4 pre-and post-operative cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) alone (Arm A) or the same regimen with RAM 8mg/kg q2w, followed by 16 cycles RAM (Arm B, FLOT-RAM). Important endpoints of phase II (exploratory) were major pathological (complete and nearly complete) response, centrally assessed acc. to Becker criteria, R0-resection rate, and safety. GEJ type I tumors and pts requiring trans-thoracic esophagectomy were excluded for safety reasons during the conduct of the study. Results: In total, 180 pts were randomized. Baseline characteristics were similar between arms (male, 73%; median age, 60y; cT3/T4, 83%; cN+, 78%; GEJ, 54%; signet-ring cells, 40%). However, the FLOT-RAM arm included more unfavorable pts with T4 (9% vs. 4%), Siewert type I tumors (18% vs. 13%), impaired ECOG PS of 1 (34% vs. 20%), and concomitant disease (87% vs. 79%). 91% of pts with FLOT and 92% with FLOT-RAM completed the 4 pre- cycles. R0-resection (in the full set) could be achieved in 83% of pts with FLOT and 97% of pts with FLOT-RAM (p = 0.0049). The rate of major path response was similar in both arms and was 30% for FLOT and 27% for FLOT-RAM. Surgical morbidity was observed in 37% of pts with FLOT and 44% of pts with FLOT-RAM. Mortality was 2.5% with FLOT and 5.9% with FLOT-RAM including GEJ type I tumors and dropped to 2.9% in both arms after excluding type I tumors per amendment. There was bit more G≥3 adverse events with FLOT-RAM (78% vs. 89%). Conclusions: In this phase II trial, the addition of ramucirumab to perioperative FLOT significantly improved R0-resection rates without an impact on path response, mainly because more patients could proceed to operation. The FLOT-RAM is safe, when type I tumors are excluded. Clinical trial information: NCT02661971.