Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in adults. The etiology of GBM is not known, and the prognosis is usually very poor. Despite new diagnostic techniques and treatment methods, the management of patients with GBM is difficult. Currently, the standard of care for the treatment of GBM is surgical resection, followed by concurrent RT with temozolomide, completed by adjuvant CT with temozolomide. Despite the survival benefit associated with these treatments, the majority of patients relapse following initial therapy. Unfortunately, optimal management for patients with recurrent or progressive GBM is unclear. In general, treatment for recurrent GBM may involve repeated resection, focal irradiation, and systemic therapies. When considering in terms of chemotherapy regimen, bevacizumab and irinotecan combination therapy for the progressive GBM may be used a suitable regimen. Also complete response in case of recurrent GBM is very rare. We present two cases with GBM who had complete response with bevacizumab plus irinotecan as second-line CT regimen, which rapidly progressed after surgery, chemoradiotherapy (CRT) and first-line temozolomide therapy. Signs of rapid proliferation in the pathologic specimen of both cases were recorded. During follow-up both cases developed recurrent tumor within a month after first three cycles first-line temozolomide CT.