Advanced central nervous system (CNS) lymphoma is an exclusion criterion for most chimeric antigen receptor (CAR) T-cell studies due to the associated levels of neurotoxicity. In this study, we described five patients with chemorefractory B-cell CNS lymphoma who received CAR19 and CAR22 T-cell "Cocktail" therapy and follow-up for 6-16 months. All patients experienced cytokine release syndrome (CRS). Two patients experienced CAR T-cell-related encephalopathy syndrome (CRES), which was controllable. The best response was observed in two patients, who successfully achieved complete remissions (CR), and the other three patients achieved partial remissions (PR). Four patients had progressive disease (PD) after remission. In addition, one CR patient and one PD patient accepted CAR T-cell infusion following hematopoietic stem cell transplantation therapy in the 3rd month and were in ongoing remission for 14 and 6 months of follow-up, respectively. The targeted antigens in two patients were still positive, and CAR T-cells were reboosted in the cerebrospinal fluid (CSF) after PD, but a small number of CD3-positive T-cells were observed to infiltrate into the tumor. Our study indicates the efficacy of CAR T-cell therapy for CNS lymphoma with an acceptable safety profile; however, the remission did not last long, perhaps due to the tumor immunosuppressive microenvironment (TME) of the CNS. CAR T-cell therapy should be combined with other treatments to help improve the TME of cerebral lymphoma.