The bus was heading to Anba Samuel monastery in the Minya Governorate, 250km south of Cairo.
Twenty-three Christians were killed and twenty five others injured, according to the Ministry of Health.
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The ambulances rushed to the place of the incident to transfer injured to hospitals.
There have been a number of attacks on Copts in the country in recent months claimed by Islamic State (IS) militants.
Two suicide bombings targeting churches in Tanta and Alexandria on April 9 left at least 46 people dead.
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