Although oral targeted therapies have improved the treatment of mantle cell lymphoma (MCL), outcomes remain poor. We recently showed that an oral form of Bendamustine works as well as the intravenous version. In this study, we tested its effect—alone or in combination with two other oral drugs, Venetoclax and Acalabrutinib—on two human MCL cell lines. We found that oral Bendamustine strongly reduced tumor growth and improved survival in mice with human MCL, performing better than the other single treatments. When combined with Venetoclax, with or without Acalabrutinib, its anti-tumor effect was even stronger in a cell line-dependent manner. These findings support further investigations of oral Bendamustine as a treatment option in MCL.