The now famous photo was taken during a speech in the capital, Bangui, and has been tweeted more than 100,000 times.
Tweeters have been making thousands of imaginary rap lyrics, known as bars, under the hashtag #PopeBars.
The Pope was in the CAR as part of a three-nation tour to Africa which also took him to Kenya and Uganda.
The visit was Pope Francis' first to the continent and he spent six days in the three countries where he was greeted by thousands of the faithful.
In Bangui he also addressed Muslim worshippers in a mosque where he said that "Christians and Muslims are brothers and sisters".
The country has experienced after nearly three years of violence between Christians and Muslims.
After the Pope left the CAR for Rome, Twitter users began to imagine what subjects the pontiff could be rapping about:
Read more about the Pope's visit to Africa:

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The Conservatives, now with a majority at Westminster, have pledged to replace the Act with a British Bill of Rights.
They want to give UK courts and Parliament the "final say" on human rights issues rather than Strasbourg.
Asked about the impact of such a change on Wales, Mr Jones told assembly members: "It would make us look like a Banana republic, frankly."
The Human Rights Act came into force in 2000, bringing the rights contained in the European Convention on Human Rights into UK law.
Critics say the Act has led to "perverse" judgements, including a ruling that found the UK's blanket ban on prisoners voting was unlawful.
But during Tuesday's First Minister's Questions, Mr Jones said: "Most countries in Europe including Russia are signatories, are members of the European Convention.
"The European Convention was drafted by British lawyers; it's a British invention, and there's a complete lack of understanding of history in Whitehall at the moment," Mr Jones added.
Under the Conservatives' plan, the European Courts would not be able to require the UK to change British laws, with its judgements being treated as "advisory" rather than binding.
Instead, the UK's Supreme Court would be "the ultimate arbiter" on human rights matters.
Welsh Liberal Democrat leader Kirsty Williams accused Conservative ministers of wanting to "put us in the same category as Kazakhstan in terms of how we view human rights".
"Liberal Democrats stopped the Tories scrapping the Human Rights Act and we are determined to keep fighting these plans," she said.
The European Convention created basic human rights and freedoms for every citizen in Europe.
They include the rights to life, liberty and security, a fair trial, respect for private life, and freedom of expression.
A Ministry of Justice spokesman said: "The Government was elected with a manifesto commitment to replace the Human Rights Act with a British Bill of Rights.
"Ministers will be discussing their plans on this and making announcements in due course."
A photo of Pope Francis has gone viral on social media after he was captured in a classic rapper pose during a visit to the Central African Republic (CAR).
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Nigeria's commercial capital, Lagos, has had a makeover over the last decade, as this gallery from the BBC's Ayo Bello shows:
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Scrapping the Human Rights Act would "make us look like a banana republic", First Minister Carwyn Jones has warned.