Background: HDC is curative therapy for relapsed GCT. The Beyer model identifies groups with poor (5% EFS at 1-year post-HDC), intermediate (25% EFS), or good risk (≥50% EFS). Given high VEGF expression in metastatic GCT and BEV-chemotherapy synergy, we studied concurrent BEV/HDC and the efficacy of a novel regimen of infusional gemcitabine, docetaxel, melphalan, carboplatin (GDMC) (BBMT 2005;11:297) in refractory GCT. Methods: Eligibility: GCT in poor/interm-risk 1t relapse or in ≥2nd relapse. Patients (pts) received tandem HDC/ASCT with BEV (5 mg/kg) 1 week before each cycle. HDC#1: GDMC; HDC#2: ifosfamide/carboplatin/etoposide. Trial powered to distinguish an expected 1-yr EFS of 15% from a goal of 50%. Results: We treated 42 pts, median age 22 (19-45) (Table). HDC#1 main toxicities: mucositis (31 G3, 11 G2) and rash (3 G3, 12 G2). Among 7 pts with marginal renal function, there were 4 HDC-related deaths (3 sepsis, 1 fungal pneumonia). Protocol was amended to reduce HDC doses by 15% in 8 subsequent pts with high creatinine (1.5–1.8 mg/dl), with no more deaths. Tumor markers normalized in 83% pts. Surgery of residual lesions (N=9) showed necrosis (5), mature teratoma (1), necrosis+teratoma (2) and teratocarcinoma (1). Median follow-up from HDC#1 for alive pts is 22 (1-69) months. The 1- and 2-yr EFS rates are both 63% (95% CI, 49-81%). The 1- and 2-yr OS rates are 72% (59-89%) and 65% (50-84%), respectively. Conclusions: Tandem HDC with BEV/GDMC followed by BEV/ICE showed promising EFS in pts with heavily pretreated and refractory GCT, exceeding the expected results with carboplatin/etoposide and no BEV, and warrants testing in less heavily pretreated pts. Clinical trial information: NCI-2011-01631.